title: Bone metastasis from breast cancer involves elevated IL-11 expression and the gp130/STAT3 pathway.
abstract: To evaluate the relationship between IL-11 and bone metastasis in patients with breast cancer and explore the potential molecular mechanism, total serum samples were collected from 180 breast cancer patients and 20 women without breast cancer. The serum expression level of interleukin (IL)-11, connective tissue growth factor (CTGF), transforming growth factor-β, and Tracp5b was determined by enzyme-linked immunosorbent assay, and mRNA expression of IL-11 in fresh breast cancer tissue was determined by RT-PCR. Immunohistochemical staining was used to detect the expression of IL-11 and CTGF in breast cancer tissue, and Western blot was used to detect the expression of p-38, p-C-JUN, p-STAT3, and p-gp130 in fresh breast cancer tissue. DNA-binding activity of AP-1 was examined by electrophoretic mobility shift assay. Differences were statistically analyzed between the group with breast cancer metastatic to bone (MBC-B) and the group with only primary breast cancer (PBC). Serum level and mRNA expression of IL-11 in the MBC-B group were significantly higher than those in the PBC group. IL-11 immunohistochemical staining showed that the percentage of positively stained cells in the MBC-B group (57.5 %) was significantly higher than that in the PBC group (14.29 %). Western blot analysis showed higher expression of p-p38, p-C-JUN, p-STAT3, and p-gp130 in the MBC-B group than in the PBC group. DNA-binding activity of AP-1 was significantly higher in the MBC-B group than in the PBC group. These data suggest that IL-11 is associated with bone metastasis and may be of value for predicting bone metastasis from breast cancer.
authors.affiliation: Department of Laboratory, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China. roland-li@163.com
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Zuoliang
authors.initials: Z
authors.lastname: Dong
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Shiwu
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D055513:Connective Tissue Growth Factor / Q000235:genetics; D050822:Cytokine Receptor gp130 / Q000235:genetics*; D005260:Female; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics*; D000071681:Tartrate-Resistant Acid Phosphatase; D018808:Transcription Factor AP-1 / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics
chemical_list: C508611:IL11 protein, human; D017370:Interleukin-11; D007527:Isoenzymes; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; D050822:Cytokine Receptor gp130; D055513:Connective Tissue Growth Factor; D048051:p38 Mitogen-Activated Protein Kinases; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase